Table 1.
Key clinical trials in metastatic/unresectable melanoma.
| Trial/Year | Design (n) | Intervention | Stage (AJCC 7th edition) | PFS | Response rate | Overall survival | Treatment related adverse events |
|---|---|---|---|---|---|---|---|
| MDX010-20 2010 (113) | Phase III (n=540) | Ipilimumab (3 mg/kg) + gp100 vaccine every 3 weeks for 4 doses (n=403) vs ipilimumab (3 mg/kg) every 3 weeks for 4 doses (n=137) vs gp100 vaccine (n=136) | Stage IV | Median PFS Ipilimumab-gp100 2.76 months (95% CI, 2.73 to 2.79) vs ipilimumab 2.86 months (95% CI, 2.76 to 3.02) vs gp100 2.76 months (95% CI, 2.73 to 2.83) |
Ipilimumab-gp100 5.7% (3.7-8.4; p=0.04) vs ipilimumab 10.9% (6.3-17.4; p = 0.001) vs gp100 1.5% | Median OS 10.0 months ipilimumab-gp100 vs 10.1 months (95% CI, 8.0-13.8) ipilimumab vs 6.4 months (95% CI, 5.5-8.7) gp100 (0.2-5.2) | Grade 3-4 Ipi + gp100: 17.4% Ipilimumab: 22.9% gp100: 11.4% |
| CA184-024 2011 (114) | Phase III (n=502) | Ipilimumab (10 mg/kg) + dacarbazine (850 mg/m2) for 4 doses then dacarbazine monotherapy for another 4 doses (n=250) vs dacarbazine (850 mg/m2) (n=252) | Stage IV | Not reported | Ipilimumab + dacarbazine 15.2% vs dacarbazine 10.3% | Median OS Ipilimumab-dacarbazine 11.2 months (95% CI 9.4 to 13.6) vs dacarbazine 9.1 months (95% CI, 7.8-10.5) | Grade 3-4 any cause AE Ipilimumab-Dacarbazine: 56.3% Dacarbazine: 29.4% |
| CHECKMATE-067 2015 (1, 117) | Phase III (n=1296) | Ipilimumab (3 mg/kg) + nivolumab (1 mg/kg) every 3 weeks for 4 doses then nivolumab (n=314) vs nivolumab (3mg/kg) every 2 weeks (n=316) vs ipilimumab (3mg/kg) every 3 weeks for 4 doses + placebo (n=315) | Unresectable Stage III or IV | Median PFS Ipi-nivo 11.5 months (95% CI, 8.7 to 19.3) vs nivolumab 6.9 months (95% CI, 5.1 to 9.7) vs ipilimumab 2.9 months (95% CI, 2.8 to 3.2) Ipi-nivo vs ipi HR=0.42, (95% CI, 0.35 to 0.51) p< 0.0001 Nivolumab vs ipi HR=0.53, (95% CI 0.44 to 0.64, p< 0.0001 Ipi-nivo vs nivo HR= 0.79, (95% CI, 0.65 to 0.97) (post hoc) |
Ipi-nivo 58% vs nivolumab 44% vs ipiliumumab 19% | Minimum follow-up of 6.5 years: median OS ipi-nivo 72.1 months (38.2-NR) vs nivolumab 36.9 months (28.2-NR) vs ipilimumab 19.9 months (16.8-24.6) | Grade 3-5 Ipi-nivo: 59% Nivolumab: 21% Ipilimumab: 28% |
| KEYNOTE-006 2015 (116) | Phase III (n=834) | Pembrolizumab (10 mg/kg) every 2 weeks (n=279) or every 3 weeks (n=277) vs ipilimumab 3 mg/kg every 3 weeks for 4 doses (n=278) | Unresectable stage III or IV | Median PFS Combined pembrolizumab groups 8.4 months (95% CI, 6.6–11.3) vs ipilimumab 3.4 months (2.9–4.2) HR=0.70, (95% CI, 0.48–0.67), p<0.0001 |
Pembrolizumab 33.7% every 2 weeks (p<0.001 vs ipilimumab), pembrolizumab every 3 weeks 32.9% (p<0.001) vs 11.9% for ipilimumab | Median OS Combined pembrolizumab groups 32.7 months (95% CI, 24.5–41.6) vs ipilimumab 15.9 months (95% CI, 1.3–22.0) HR=0.73, (95% CI, 0.61–0.88), p=0.00049 |
Grade 3-5 Pembrolizumab every 2 weeks: 13.3% Pembrolizumab every 3 weeks: 10.1% Ipilimumab: 19.9% |
| CA184-169 2017 (118) | Phase III (n=727) | Ipilimumab (10 mg/kg) (n=365) vs ipilimumab (3 mg/kg) (n=362) every 3 weeks for 4 doses | Unresectable stage III or IV | Median PFS Ipilimumab 10 mg/kg 2.8 months (95% CI, 2.8–3.0) vs ipilimumab 3 mg/kg 2.8 months (2.8–2.8) HR=0.89 (95% CI, 0.76–1.40), p=0·16 |
Ipilimumab 10 mg/kg 15% (11.8-19.5) 10mg/kg vs ipilimumab 3mg/kg 12% (9.0=-16.0) | Median OS Ipilimumab 10 mg/kg 15.7 months (95% CI, 11.6 to 17.8) vs Ipilimumab 3 mg/kg 11.5 months (95% CI, 9.9 to 13.3) HR=0.84, (95% CI, 0.71 to 0.99), p=0.04 |
Grade 3-5 Ipilimumab (10mg/kg): 43% Ipilimumab (3 mg/kg): 18% |
| RELATIVITY-047 2022 (19, 119) |
Phase II/III (n=714) | Relatlimab (160 mg) + nivolumab (480 mg) every 4 weeks (n=355) vs nivolumab (480 mg) every 4 weeks (n=359) | Unresectable stage III or IV* | Median PFS Rela-nivo 10.1 months (95% CI, 6.4 to 15.7) vs nivolumab 4.6 months (95% CI, 3.4 to 5.6) HR=0.78, (95% CI, 0.64-0.94) |
Rela-nivo 43.1% (95% CI, 37.9-48.4) vs nivolumab 32.6% (95% CI, 27.8-37.7) | Median OS not reached for rela-nivo vs nivolumab 34.1 months HR=0.80, (95% CI, 0.64-1.1) p = 0.0593 |
Grade 3-5 Rela-nivo: 19.7% Nivolumab: 10.3% |
ipi-nivo, combination ipilimumab-nivolumab; ORR, overall response rate; HR, hazard ratio; TRAE, treatment related adverse events; rela-nivo, combination relatlimab-nivolumab; *Enrollment based upon AJCC 8th edition.
Table lists trials and the year they were conducted, trial design and intervention, stage of disease and key outcomes such as progression-free survival (PFS), response rates, overall survival (OS) and any significant toxicity. Stage as per American Joint Committee on Cancer (AJCC) 7th edition unless otherwise noted.